IL-20 activates human lymphatic endothelial cells causing cell signalling and tube formation

Area of Science:

• Vascular Biology
• Cell Signaling
• Lymphatic System Development

Background:

• Interleukin-20 (IL-20) is known for its role in arteriogenesis and cellular organization.
• Its function in lymphangiogenesis, the formation of new lymphatic vessels, remains largely unexplored.

Purpose of the Study:

• To investigate the role of IL-20 in lymphangiogenesis using a human lymphatic endothelial cell line.
• To elucidate the signaling pathways activated by IL-20 in lymphatic endothelial cells.

Main Methods:

• Utilized the hTERT-HDLEC cell line expressing lymphatic markers LYVE-1 and podoplanin.
• Stimulated cells with IL-20 and analyzed intracellular calcium, protein phosphorylation (Akt, eNOS, Erk1/2, mTOR), and nitric oxide (NO) production.
• Assessed cell proliferation, actin polymerization, tube formation in matrigels, and cell migration using specific inhibitors (PD98059, rapamycin, wortmannin).

Main Results:

• IL-20 stimulation increased intracellular calcium, Akt/eNOS phosphorylation, and NO production, dependent on the PI3K/Akt pathway.
• IL-20 induced Erk1/2 and mTOR phosphorylation, crucial for proliferation.
• IL-20 triggered actin polymerization, cell elongation, tube formation, and cell migration comparable to VEGF-C, dependent on PI3K and mTOR signaling.

Conclusions:

• IL-20 activates key cell signaling pathways, including PI3K/Akt, Erk1/2, and mTOR.
• These pathways mediate IL-20-induced lymphangiogenic processes: proliferation, migration, and tube formation.
• IL-20 is identified as a significant cytokine capable of activating or modulating lymphatic vessel formation.